Our long-term goal is to study the role of tissue degradation in abnormal growth of human prostate, namely, benign prostatic hyperplasia and prostatic carcinoma. The present proposal represents the initial effort of our long-range objective and is dealing with the area of basic biology of prostatic regression, using rat prostate as the study system. Since the prostate is androgen-dependent, withdrawal of this hormone by castration in the animal results in rapid regression of the prostate. The assumption is that tissue breakdown is caused by the action of degradative enzymes such as nucleases and proteases. The objective of the present proposal is to attempt to answer the following questions: (1) Is the regressing prostate able to synthesize degradative enzymes (or some factors responsible for degradative processes)? (2) Does prostatic involution involve the activation of pre-existing enzymes in the tissue? (3) If one or both of the above possibilities are operating in the rat prostate during its regression, can the process be modified? The following techniques will be (or already have been) developed for this study: (1) In vitro incorporation of 3H-leucine by prostatic tissue and subsequent release of radioactivity from the tissue, (2) measurement of activities for cathepsin D and RNase in prostatic tissue, and (3) isolation of mRNA from regressing rat prostate and the subsequent determination of cathepsin D and RNase in the protein synthesized in a cell-free system by the isolated mRNA. The following experiments will be carried out during the period of proposed project: (1) Effects of testosterone at different stages of prostatic regression on the above parameters, (2) effect of actinomycin D and cycloheximide on prostatic regression, and (3) effect of chloroquine and vitamin A.